EBioMedicine
Authors: Kalen J Petersen, Seungjae Kim, Pete Canfield, June Roman, Sarah A Cooley, Manjula Bhuma, Adam Anderson, Brittany Nelson, Patricia Reid, Elizabeth Westerhaus, Maurizio Caocci, Tricia H Burdo, Aristeidis Sotiras & Beau M Ances
In this study, the authors investigated the relationship between epigenetic markers of biological aging, brain health, and social determinants of health among people with and without HIV. The case-control study included 126 people with HIV (PWH) receiving effective antiretroviral therapy and 145 people without HIV. Participants underwent blood collection, brain magnetic resonance imaging (MRI), and neuropsychological testing. Investigators evaluated four DNA methylation-based measures: GrimAge, PhenoAge, DunedinPACE, and predicted telomere length, examining their associations with brain structure, cognitive performance, and social and clinical risk factors.
After adjusting for demographic factors, PWH exhibited significantly greater biological aging, reflected by elevated GrimAge (+1.8 years), PhenoAge (+2.4 years), and DunedinPACE (5.1% higher aging rate), alongside shorter predicted telomere length. GrimAge was also associated with brain age gap, with each decade increase in GrimAge corresponding to a 5.9-year increase in estimated brain age. Epigenetic aging measures were associated with poorer performance in specific cognitive domains. Among PWH, greater neighborhood socioeconomic deprivation was associated with higher GrimAge, whereas higher educational attainment was associated with lower GrimAge. Cardiovascular risk was associated with increased GrimAge across both groups.
Overall, the findings suggested that accelerated biological aging may persist in people with HIV despite viral suppression and may be associated with brain structural changes and cognitive dysfunction. The study highlighted the potential utility of epigenetic clocks as biomarkers of neurological aging and underscored the importance of addressing modifiable clinical and socioeconomic factors to support healthy aging among people living with HIV.